Neural induction is one of the most important processes during vertebrate embryonic development, both because it is one of the earliest interactions between defined groups of cells in the normal embryo, and because this event initiates the development of the adult Central Nervous System (CNS). It was first described as an interaction between two groups of cells: the "organizer" (which emits inducing signals) and the ectoderm (which responds to them by giving rise to the neural plate proper and to neural crest cells). Neural induction also initiates the regional subdivision of the CNS. Neural inducing signals are not confined to the organizer; the young neural plate itself can induce a neural plate from competent ectoderm ("homeogenetic induction"). Surprisingly, this phenomenon has not yet been studied in detail, and it is not even known whether homeogenetic induction is region-specific (for example: does forebrain induce forebrain?). Attempts to understand the molecular mechanisms of neural induction and regionalization in different species of vertebrates have produced contradictory results. However, the notion is starting to emerge that cooperation between several signaling pathways is involved in neural induction and the early patterning of the nervous system. In this project we will use a combination of molecular and embryological methods to investigate the earliest events leading to the induction and regionalization of the nervous system. Specifically, the aims are: A. To address the questions: Is the molecular mechanism of homeogenetic induction similar to induction by the organizer? Is homeogenetic induction region-specific? B. To characterize the regulation of 6 newly-identified genes that mark early responses of the ectoderm to grafts of the organizer (Hensen?s node) by different tissues and various secreted factors, and to begin to assess their functional roles in the neural induction process. C. To study the role of the novel Zinc finger gene Churchill in neural development by targeted inactivation in mouse. D. To explore the possible roles of 6 newly-identified candidate secreted factors in the early steps of neural induction and homeogenetic induction.